Exploring Cognitive and Affective Outcomes Following Bilateral 6-Hydroxydopamine Lesions of the Substance Nigra or Striatum in Rats

Abstract

The majority of animal models of Parkinson's disease (PD) focus on motor symptoms that are induced by unilateral injections of such neurotoxins as 6-hydroxydopamine (6-OHDA) in nigrostriatal dopaminergic pathways. However, motor changes that are induced by unilateral 6-OHDA injections may interfere with the identification of cognitive and affective dysfunctions induced by dopaminergic neurodegeneration. To select an appropriate method for studying nonmotor symptoms of PD and potential neuroprotective treatments, the present study compared behavioral effects of bilateral 6-OHDA infusions directly in the substantia nigra pars compacta (SNpc) or striatum in rats. A battery of behavioral tests, including affective and cognitive tasks, was performed for 22 days after 6-OHDA nigrostriatal lesions. The massive degeneration of tyrosine hydroxylase-immunoreactive neurons was observed in the SNpc, striatum, and ventral tegmental area with 6-OHDA infusions in either the SNpc or striatum. Concerning functional outcomes, 6-OHDA infusions in the striatum decreased general exploratory activity 7 days after the lesion. Rats that received 6-OHDA in the SNpc exhibited cognitive impairments and despair-like behavior. A decrease in the number of newborn neurons was found in the hippocampus in rats that received 6-OHDA in the striatum, indicating a alteration of neuron maturation. 6-OHDA infusions in both the SNpc and striatum impacted the maturation of newborn hippocampal neurons. These results indicate that bilateral injections of 6-OHDA in the SNpc might be useful for studying nonmotor symptoms of PD.